Results of Retrospective Chart Review to Determine Improvement in Lipid Goal Attainment in Patients Treated by High-Volume Prescribers of Lipid-Modifying Drugs

BACKGROUND: There is a primary focus in cholesterol management on the elevated low-density lipoprotein cholesterol (LDL-C) component of dyslipidemia and a secondary focus on the other components of dyslipidemia, such as low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TGs), and high non-HDL-C. OBJECTIVES: This was a physician practice analysis to examine the real-world therapeutic management of patients diagnosed with hyperlipidemia and/or hypercholesterolemia according to the guidelines of the National Cholesterol Education Program (NCEP) Adult Treatment Panel Third Report (ATP III) and the American Heart Association (AHA). Additionally, the number of patients who should be diagnosed with mixed hyperlipidemia instead of hyperlipidemia or hypercholesterolemia was estimated. METHODS: A total of 600 high-volume prescribers of lipid-modifying drugs were identified in 6 metropolitan areas using the IMS Health prescription database. A total of 101 physician prescribers (about 17%) agreed to participate in the study and had the necessary medical records available. The participating prescribers were asked to identify all patients aged between 18 and 79 years who were seen in their practice in the last 2 years having a diagnosis of hyperlipidemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 272.4) and/or hypercholesterolemia (ICD-9-CM code 272.0). ICD-9-CM code 272.2 (mixed hyperlipidemia) was purposely excluded from the criteria for patient chart selection in order to estimate the prevalence of mixed hyperlipidemia in patients previously diagnosed with hyperlipidemia and/or hypercholesterolemia. A random number generator was used to select 25 patient medical records from each office. A common instrument was used to collect data on patient demographics; clinical history; comorbid disease states; laboratory test results, including liver function; and 4 values for serum cholesterol (total cholesterol, LDL-C, HDL-C, TG). Total cholesterol was recorded to permit calculation of non-HDL-C. Data collection via patient chart abstraction occurred from March 2004 through August 2004, performed by a staff member in each physician practice who had been trained for this purpose. Drug prescribing was identified from the patient chart. RESULTS: For the physician practice assessment portion of the project, we used patient charts if there was a complete (total cholesterol, TG, HDL-C, and LDL-C) lipid profile for baseline and follow-up, and a minimum of 6 weeks between baseline and follow-up values. At follow-up, the proportion of patients meeting goal lipid values according to the guidelines for LDL-C was 68%, 63% for HDL-C, 59% for TG, and 68% for non-HDL-C. Only 32% of patients met all 3 goals (LDL-C, HDL-C, and TG). The average time between the baseline and follow-up lipid profile was 3.7 years, with a median of 2.9 years, and a minimum of 6 weeks and a maximum of 42 years. Compared with baseline, the most recent follow-up lipid assessment for HDL-C goal attainment showed improvement by an absolute 6%, from 57% to 63% of patients. TG goal attainment improved an absolute 18% (from 41% to 59%), LDL-C goal attainment improved an absolute 45% (from 23% to 68%), non-HDL-C goal attainment improved an absolute 46% (from 22% to 68%), and the combined goals of LDL-C, HDL-C, and TG improved from 8% of patients at baseline to 32% at follow-up. Of the 2,119 patients in the study population, 1,784 (84%) at the time of chart review had been prescribed at least 1 lipid-modifying medication: 1,552 (87%) a single lipid modifying medication and 232 (13%) combination therapy. The hydroxymethylglutaryl (HMG) coenzyme-A reductase class (statins) accounted for 89% of the monotherapy regimens. Of the patients with baseline LDL-C, HDL-C, and TG readings, 40% could have been diagnosed as having mixed hyperlipidemia, defined as having (a) baseline LDL-C, HDL-C, and TG readings, 40% could have been diagnosed as having mixed hyperlipidemia, defined as having (a) baseline LDL-C greater than their NCEP ATP III goal and (b) either baseline TG of greater than150 mg/dL or a baseline HDL-C of less than 40mg/dL for males or less than 50 mg/dL for females. Of the 40% of patients estimated to have mixed hyperlipidemia, 69% were prescribed lipid-modifying monotherapy, 18% were prescribed combination drug therapy, and 14% were not prescribed drug therapy. CONCLUSIONS: Attainment of therapeutic goals for serum lipids improved from baseline to follow-up, but approximately one third of patients did not achieve individual lipid goals and two thirds of patients did not attain goal for all 3 argets (LDL-C, HDL-C, and TG).

METHODS: A total of 600 high-volume prescribers of lipid-modifying drugs were identified in 6 metropolitan areas using the IMS Health prescription database. A total of 101 physician prescribers (about 17%) agreed to participate in the study and had the necessary medical records available. The participating prescribers were asked to identify all patients aged between 18 and 79 years who were seen in their practice in the last 2 years having a diagnosis of hyperlipidemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 272.4) and/or hypercholesterolemia (ICD-9-CM code 272.0). ICD-9-CM code 272.2 (mixed hyperlipidemia) was purposely excluded from the criteria for patient chart selection in order to estimate the prevalence of mixed hyperlipidemia in patients previously diagnosed with hyperlipidemia and/or hypercholesterolemia. A random number generator was used to select 25 patient medical records from each office. A common instrument was used to collect data on patient demographics; clinical history; comorbid disease states; laboratory test results, including liver function; and 4 values for serum cholesterol (total cholesterol, LDL-C, HDL-C, TG). Total cholesterol was recorded to permit calculation of non-HDL-C. Data collection via patient chart abstraction occurred from March 2004 through August 2004, performed by a staff member in each physician practice who had been trained for this purpose. Drug prescribing was identified from the patient chart.
RESULTS: For the physician practice assessment portion of the project, we used patient charts if there was a complete (total cholesterol, TG, HDL-C, and LDL-C) lipid profile for baseline and follow-up, and a minimum of 6 weeks between baseline and follow-up values. At follow-up, the proportion of patients meeting goal lipid values according to the guidelines for LDL-C was 68%, 63% for HDL-C, 59% for TG, and 68% for non-HDL-C. Only 32% of patients met all 3 goals (LDL-C, HDL-C, and TG). The average time between the baseline and follow-up lipid profile was 3.7 years, with a median of 2.9 years, and a minimum of 6 weeks and a maximum of 42 years. Compared with baseline, the most recent follow-up lipid assessment for HDL-C goal attainment showed improvement by an absolute 6%, from 57% to 63% of patients. TG goal attainment improved an absolute 18% (from 41% to 59%), LDL-C goal attainment improved an absolute 45% (from 23% to 68%), non-HDL-C goal attainment improved an absolute 46% (from 22% to 68%), and the combined goals of LDL-C, HDL-C, and TG improved from 8% of patients at baseline to 32% at follow-up. Of the 2,119 patients in the cholesterol (HDL-C), and high triglyceride (TG) levels have all been clearly demonstrated to be independently associated with increased CHD risk. [4][5][6] Multiple guidelines for the treatment of dyslipidemia and the prevention of CHD have been published. These include the National Cholesterol Education Program (NCEP) Adult Treatment Panel Third Report (ATP III), American Heart Association (AHA) (for women, 2004), American Diabetes Association, and American Association of Clinical Endocrinologists guidelines. 3,[7][8][9] Total Therapeutic Management, a disease management and health care research organization, was engaged by the sponsor of this study to examine the real-world therapeutic management of elevated LDL-C, HDL-C, TG, and non-HDL-C levels individually and in combination (mixed hyperlipidemia) against NCEP ATP III and AHA guidelines in patients diagnosed with hyperlipidemia and/or hypercholesterolemia ( Table 1). The sponsor was also interested in the proportion of patients who did not have a diagnosis or diagnosis code for mixed hyperlipidemia but who might be classified more accurately as having mixed hyperlipidemia.
Review by an institutional review board was not sought for this study since the abstracted data delivered to the authors were deidentified with no opportunity to trace the data back to individual patients.

ss Methods
A total of 600 of the highest-volume prescribers of lipid-modifying drugs, 100 each from 6 metropolitan service areas (Atlanta, Georgia; Cleveland, Ohio; Milwaukee, Wisconsin; New York, New York; San Francisco, California; and Seattle, Washington) were identified from the IMS Health prescription database (Table 2). Each provider was given 6 months to return the completed 25 patient data abstraction forms. In total, 103 prescribers (17 from Atlanta, 20 from Cleveland, 20 from Milwaukee, 13 from New York, 15 from San Francisco, and 18 from Seattle) agreed to participate, had at least 25 patients meeting the inclusion criteria, and returned their completed data abstraction forms in the required timeframe. In return, each provider received feedback on the comparison of their practice with other practices and national guidelines. No compensation was provided to the participating prescribers or to their office staff. Two prescribers in the New York metropolitan area did not have complete baseline and follow-up lipid profiles for their patients and were excluded from the results, leaving 101 physician practices (Table 2), approximately 17% of original samples.
The prescribers were asked to identify, by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) billing codes, all patients aged between 18 and 79 years who were seen in their practice in the last 2 years having a diagnosis of hyperlipidemia (ICD-9-CM code 272.4) and/or hypercholesterolemia (ICD-9-CM code 272.0). ICD-9-CM code 272.2 (mixed hyperlipidemia) was purposely excluded from the criteria for patient chart selection to permit estimation of the proportion of patients who did not have a diagnosis or diagnosis code for mixed hyperlipidemia but who might be classified more accurately as having mixed hyperlipidemia.
On the basis of the number of patients identified by each practice meeting the aforementioned criteria, we developed a random number list using SAS v8.2 statistical software (SAS Institute, Inc., Cary, NC). We then ranked the identified patients alphabetically by last name and numbered sequentially for each physician practice. Using the random number list specific to that physician practice, we selected 25 patients for medical record review. Of the total 2,525 patient charts from 101 physician practices, 406 (16%) had an incomplete lipid profile for baseline and follow-up or more than 6 weeks between baseline and follow-up lipid values; therefore, the sample size for analysis was 2,119 patients ( Table 2).
One staff member from each physician practice reviewed these medical records using a standardized data collection form. The data abstractor from each physician practice received uniform verbal and written directions on how to complete the data collection form. This data collection form was designed to gather information on patient demographics, clinical history, comorbid disease states, laboratory test results (total cholesterol, LDL-C, HDL-C, TG, and liver function tests) and cholesterol drug therapy pertinent to the management of dyslipidemia. Non-HDL-C was calculated from the difference between total cholesterol and the HDL-C value. Patient inclusion criteria required new starts to cholesterol drug therapy or at least a 6-week washout period from previous cholesterol medications before starting current cholesterol medications. Also, baseline lipid values were recorded at least 6 weeks before the initiation of cholesterol drug therapy or 6 weeks free of cholesterol drug therapy, whichever was more recent. Follow-up values were the most recent lab values from the date of data abstraction but at least 6 weeks after baseline. Data abstraction occurred in physician offices from March 2004 through August 2004.

CHD Risk Factors, Risk Equivalents, and Optimal Lipid Values Based on NCEP ATP III and AHA Guidelines
The medical record for each patient was reviewed to determine individual goal values for LDL-C, non-HDL-C, and TG based on the NCEP ATP III guidelines. Goal HDL-C was determined from the NCEP ATP III (men) or AHA (women) guidelines. The NCEP ATP III guidelines were chosen for men because they are the most widely publicized and used cholesterol management guidelines, and the AHA guidelines were chosen for women because they are the most specific for women. The appropriate

Results of Retrospective Chart Review to Determine Improvement in Lipid Goal Attainment in Patients Treated by High-Volume Prescribers of Lipid-Modifying Drugs
optimal values were determined by assessing the presence of CHD, CHD risk factors, and CHD risk equivalents. CHD was defined as a notation in the patient chart of CHD, myocardial infarction (MI), angina, angioplasty, or bypass surgery. The definition of risk factors and risk equivalents along with definitions of optimal values for LDL-C, HDL-C, non-HDL-C, and TG used in this study are presented in Table1.
All collected data were aggregated and analyzed, and a report using charts and graphs was developed for each prescriber' s practice. Data analysis was performed using SAS v8.2 statistical software. We performed analysis for the overall patient population and for subgroups including males, females, patients ≥65 years, CHD, diabetes mellitus, metabolic syndrome, and peripheral arterial disease.

ss Results
Among the 101 physician prescribers participating in this analysis, 82% were primary care physicians (family practice, internal medicine, or general practice), 8% were endocrinologists, 6% were cardiologists, 1% were nephrologists, and 3% were classified as other specialty.
Of the 2,119 patients included in this study, the vast majority, 79% (1,668/2,119), were treated for primary prevention (Table 3); 55% (n = 1,158) were male, 44% (n = 945) were female, and 1% (n = 16) of the population had no gender documented in their medical chart ( Table 4). The mean age and standard deviation at the time of data collection was 61 ±12 years.
Lipid values for the overall population, by gender and by age ≥65 years, are summarized in Table 4. Baseline was defined as  at least 6 weeks before prescribing or free of any lipid-modifying medication therapy for 6 weeks. The median baseline LDL-C, HDL-C, TG, and non-HDL-C values for the overall population were 154 mg/dL for LDL-C, 46 mg/dL for HDL-C, 171 mg/dL for TG, and 188 g/dL for non-HDL-C. Non-HDL-C was calculated by subtracting the HDL value from the total cholesterol value. 9 The distribution of baseline pharmacotherapy for cholesterol disorders is summarized in Table 5. A total of 335 patients (16%) received no drug therapy. Of the 1,784 patients who were prescribed lipid-modifying medication therapy, 1,552 (87%) were prescribed monotherapy and 232 patients (13%) were prescribed combination therapy. The proportion of the different lipid-modifying medications as monotherapy and as combinations was relatively the same across each category. Statins were the most widely prescribed monotherapy agent and the principal agent prescribed in combination therapy.

Baseline and Follow-up Lipid Values (N = 2,119)
Results of baseline and follow-up attainment of optimal lipid values in our study population are represented in Figure 1 and Table 4. The most recent follow-up value was defined as being the most recent complete lipid profile in the patient' s medical record at least 6 weeks after the baseline value. In general, the percentage of patients with lipid goal attainment improved from baseline to follow-up (Figure 1). Improvement in the proportion of patients at LDL-C goal appeared much larger than the proportion of patients who attained goal HDL-C and TG values at follow-up versus baseline. There was a 4-fold increase in the proportion of patients who attained goal values for all 3 serum lipids (LDL-C, HDL-C, and TG), but the absolute proportion was only 32% of patients at follow-up.

Results of Retrospective Chart Review to Determine Improvement in Lipid Goal Attainment in Patients Treated by High-Volume Prescribers of Lipid-Modifying Drugs
In our study population, 68% of patients met their LDL-C goal. This level of LDL-C goal attainment is very good compared with similar studies of this nature; however, there is room for improvement. 10 With regard to HDL-C and TG, fewer patients (63% and 59%, respectively) met their goals for these cholesterol parameters than for LDL-C. The proportion of the study population meeting all 3 lipid goals-for LDL-C, HDL-C, and TG combined was only 32%. When looking at the difference between the percentage of patients who were attaining goal for LDL-C, HDL-C, and TG at baseline and those who had obtained lipid goal at their most recent follow-up reading, we found a smaller percentage increase (6%) in the proportion of patients who were meeting their HDL-C goal. There was a modest 18% increase in the number of patients meeting their TG goal. Chi-square analysis of the differences in the number proportion of patients meeting their goal LDL-C, HDL-C, or TG value reveals that there were significant (P <0.05) differences between the baseline and follow-up proportions for all parameters of cholesterol.
When looking at the prescribed medication to treat dyslipidemia in this population, we found the majority of patients (approximately 75%) were prescribed monotherapy with lipid-modifying medication. The statin class of lipid-modifying medications accounted for 89% (1,385/1,552, Table 5) of all monotherapy cholesterol medication prescribed. The different classes of lipid-modifying medications have different effects on cholesterol parameters. The statin class of lipid-modifying medications has the greatest potential to decrease LDL-C, the fibric acid class has the greatest potential to decrease TG, and the nicotinic acid class has the greatest potential to increase HDL-C. The bile acid sequestrants and the cholesterol absorption inhibitors have a modest effect on lowering LDL-C. 3 Our analyses also revealed that 40% of the study population potentially had mixed hyperlipidemia. In the mixed hyperlipidemia population, 14% were not prescribed drug therapy; 69% were prescribed monotherapy with lipid-modifying medication, of which 82% was statin monotherapy. Since mixed hyperlipidemia is a cholesterol disorder where multiple lipid parameters are uncontrolled, the choice of a monotherapy statin or any other monotherapy lipid-modifying medication most likely will not be appropriate to get the patient to goal LDL-C, HDL-C, and TG values.
Some physicians may not be considering the entire lipid profile when selecting and monitoring lipid-modifying therapy as evidenced by (1) nearly two thirds of patients were at LDL-C goal; (69%) and HDL-C goal (63%) at follow-up, with the larger magnitude of change in the proportion of patients at LDL-C goal; (2) the prescribing of monotherapy lipid-modifying medications in the majority of the population; and (3) 40% of the study population having mixed hyperlipidemia. Although it is appropriate to adhere to treatment guidelines that uniformly recommend addressing LDL-C as a first step, it is important to realize that this should not be the last step for all patients. Clinical trials strongly support a lower rate of cardiovascular events and reduction in the progression of atherosclerosis or regression of atherosclerosis in trials incorporating HDL-C-raising and TG-lowering strategies in addition to LDL-C lowering. [11][12][13][14] There is strong epidemiological evidence supporting low levels of HDL-C as an independent risk factor for increased CHD morbidity and mortality, and a 1% increase in HDL-C is associated with a 2% to 3% decrease in CHD risk. [15][16][17][18][19] Conversely, high HDL-C levels have been shown to confer a reduced risk for CHD. It has also been shown that raising HDL-C and lowering levels of TG without lowering LDL-C reduces the rate of coronary events. 20

Limitations
Compliance with cholesterol medication was not an objective of this study, and pharmacy dispensing records were not accessed. Therefore, we could not tie actual patient use of the prescribed lipid-modifying drug therapy with the serum lipid values recorded in the patient chart. Also, data collection may have been inconsistent because we used office personnel who were familiar with the patient charts. This method of data collection pits the tradeoff of familiarity with the methods of medical chart reporting in a given office in an attempt to reduce the opportunity for missing data, with the potential inconsistency in data abstraction that can arise from using a different data abstractor in each medical office. However, this opportunity for inconsistency was minimized through the use of a detailed, uniform training process with each physician practice staff member and the use of a standard data collection tool.
In addition, we relied on medical chart documentation mostly from primary care physician offices. All information of interest may * Goal as defined in Table 1. HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TG = triglyceride.
not have been available at the primary care physician offices, such as the most recent follow-up laboratory values or additional drug therapy that might have been recorded in the office of a cardiologist to whom the patient had been referred by the primary care physician. A more comprehensive data collection method of abstracting data from multiple physician offices seeing each patient was limited by study design because of feasibility and economics. Each patient' s lifestyle, such as diet and exercise routine, was not assessed in this study. Thus, prescribing of lipid-modifying drugs was the only factor assessed in the repeated measure of patient lipid values. Patients with high risk for CHD (e.g., hyperlipidemia and/or hypercholesterolemia) will require lifestyle modifications as well as lipidmodifying medications. 7

ss Conclusions
In our study population of patients with a diagnosis of either hyperlipidemia or hypercholesterolemia, 68% met their LDL-C goal at follow-up according to NCEP ATP-III guidelines versus 23% at baseline. A slightly smaller proportion of patients met their HDL-C and TG target goals at follow-up, 63% and 59%, respectively. The proportion of the study population meeting all 3 target goals (LDL-C, HDL-C, and TG) was only 32% but improved from 8% at baseline. Approximately 65% of the study population was prescribed lipid-modifying monotherapy with a statin, 11% was prescribed combination drug therapy, and 16% was not prescribed drug therapy. About 40% of the study population was estimated to have mixed hyperlipidemia, of which 56% was prescribed monotherapy with a statin, 18% was prescribed combination therapy, and 14% was not prescribed drug therapy.

DISCLOSURES
Funding for this study was provided through a grant from Kos Pharmaceuticals to Total Therapeutic Management, Inc., employer of authors Thomas A. Stacy and Allison Egger. Stacy served as principal author of the study. Study concept and design were primarily contributed by Stacy, with input from Egger. Data collection was the work of both authors; data interpretation was primarily the work of Egger, with input from Stacy. Writing of the manuscript and its revision were primarily the work of Stacy, with input from Egger.